Summary: A recent study found that long-term high-fat food lower enjoyment from eating by lowering neurotensin, a mind protein that boosts the dopamine answer. This reduction of prize dampens the need for high-calorie foods, potentially worsening overweight by promoting habit, dreary eating.
Restoring neurotensin rates reversed this result in mice, leading to better weight control and eating habits. The findings provide new avenues for targeted treatment and reveal a mental process responsible for fat.
Important Information:
- Function of neurotensin: Obesity is associated with a decreased level of neurotensin in mental areas related to food reward.
- Restored Motivation: In obese mice, recovering neurotensin gave back food enjoyment and standardized eating habits.
- Medical Potential: Targeting neurotensin channels may lead to accurate, side-effect-free obesity treatments.
UC Berkeley Resource
The joy we experience when we eat junk food, such as the salt, sticky French fries and a juicy burger, is frequently attributed to the rise in obesity and overeating rates in our society.
But a new study by scientists at the University of California, Berkeley, suggests that delight in eating, actually eating junk food, is essential for maintaining a healthy fat in a culture that abounds with low, high-fat food.
Paradoxically, anecdotal evidence suggests that people with overweight may get less pleasure in enjoying than those of ordinary pounds. When presented with meal, brain scans of obese people reveal a design similar to that seen in pet studies: less activity in pleasure-related mind regions.
A decrease in neurotensin, a mind peptide that interacts with the dopamine network, may be the cause of this phenomenon, according to UC Berkeley researchers, as well as a possible strategy to recover eating pleasure in a way that lowers total consumption.
The investigation reveals an unknown mental process that explains why a continual high-fat diet may reduce the desire for high-fat, sugary foods, even when these foods remain readily available.
The researchers believe that obese people experience a loss of pleasure in eating as a result of prolonged consumption of high-calorie foods. Losing this joy may actually contribute to the development of obesity.
” A natural inclination toward junk food is not inherently bad — but losing it could further exacerbate obesity”, said , Stephan Lammel, a UC Berkeley professor in the Department of Neuroscience and a member of the Helen Wills Neuroscience Institute.
The researchers discovered that this effect is caused by a drop in neurotensin in a particular brain region that connects to the dopamine network. Importantly, they demonstrate that restoring neurotensin levels can promote weight loss and restore the pleasure of eating through dietary adjustments or genetic manipulations that increase neurotensin production.
” A high-fat diet changes the brain, leading to lower neurotensin levels, which in turn alters how we eat and respond to these foods”, Lammel said. ” We discovered a way to rekindle the desire for high-calorie foods, which may actually aid in weight management.”
Although research in mice doesn’t always translate to people, this finding may provide new avenues for addressing obesity by restoring food-related enjoyment and eradicating unhealthy eating habits.
” Imagine eating an amazing dessert at a great restaurant in Paris— you experience a burst of dopamine and happiness”, said Neta Gazit Shimoni, a UC Berkeley postdoctoral fellow.
This feeling is absent in mice on a high-fat diet, but it is present in mice on a normal diet. They might continue to eat out of habit or boredom rather than genuine enjoyment.
Gazit Shimoni and former UC Berkeley graduate student Amanda Tose are co-first authors, and Lammel is senior author of the study, which will be published March 26 in the journal , Nature.
solving a challenging issue in obesity research
Doctors and researchers have struggled to understand and treat obesity for decades because countless tried-and-true diets and eating regimens have failed to deliver long-term results.
The recent success of GLP-1 agonists like Ozempic, which curb appetite by increasing feelings of fullness, stands out among many failed approaches.
Lammel examines brain circuits, particularly the dopamine network, which is crucial for motivation and reward. Dopamine is frequently associated with pleasure, which strengthens our desire to engage in rewarding activities, such as consuming high-calorie foods.
While raising mice on a high-fat diet, Gazit Shimoni noticed a striking paradox: While in their home cages, these mice strongly preferred high-fat chow, which contained 60 % fat, over normal chow with only 4 % fat, leading them to gain excessive weight.
However, when they were freed from their home cages and given high-calorie treats like butter, peanut butter, jelly, and chocolate, they displayed far less desire to indulge than regular-diet mice, which devoured everything they were given.
A normal, regular-diet mouse will immediately consume these foods, according to Gazit Shimoni. ” We only see this paradoxical attenuation of feeding motivation happening in mice on a high-fat diet”.
She was able to find out why this effect had been reported in earlier studies and how it might relate to the obesity phenotype these mice had experienced.
The effects of obesity-related brain changes are reversed by recovering neurotensin.
To investigate this phenomenon, Lammel and his team used optogenetics, a technique that allows scientists to control brain circuits with light.
In obese mice, they found that the same stimulation had no effect, suggesting that something must have changed. In normal-diet mice, stimulating a brain circuit that connects to the dopamine network increased their desire to consume high-calorie foods.
They discovered that obese mice had a high level of neurotensin, which prevented dopamine from triggering the typical pleasure response in high-calorie mice.
” Neurotensin is this missing link”, Lammel said.
It typically boosts dopamine activity to increase motivation and reward. However, neurotensin is downregulated in high-fat diet mice, and they no longer have a strong desire to consume high-calorie foods, even when they are readily available.
The researchers then looked into ways to restore neurotensin levels. When obese mice were reverted to a normal diet for two weeks, their neurotensin levels were restored, their dopamine function was restored, and they started to enjoy high-calorie foods.
The mice lost weight when neurotensin levels were artificially restored using a genetic approach, as well as improved mobility and decreased anxiety. Their feeding behavior also normalized, with increased motivation for high-calorie foods and a simultaneous reduction of their total food consumption in their home cages.
” Recovering neurotensin seems to be very, very important for preventing the loss of the desire to consume high-calorie foods,” Lammel said.
It doesn’t make you immune to weight gain, but it would encourage healthy eating habits and restore it to normal.
Toward more precise treatments for obesity
Although directly administrating neurotensin may theoretically help obese people toregain their appetite for food, it also acts on numerous brain regions, increasing the risk of unintended side effects.
The researchers used gene sequencing, a method that allowed them to identify specific genes and molecular pathways that regulate neurotensin function in obese mice, to overcome this.
This discovery provides crucial molecular targets for future obesity treatments, paving the way for more precise therapies that could selectively enhance neurotensin function without broad systemic effects.
” We now have the entire genetic makeup of these neurons and how they change with high-fat diets,” Lammel said.
” The next step is to look for precise therapeutic targets upstream and downstream of neurotensin.
Lammel and Gazit Shimoni plan to expand their research to explore neurotensin’s role beyond obesity, investigating its involvement in diabetes and eating disorders.
” The bigger question is whether these systems interact with various circumstances,” Gazit Shimoni said.
” How dopamine circuits get affected by starvation?” What happens in eating disorders? We’ll be focusing on these questions next.
Other co-authors include Byung Kook Lim of UC San Diego, Yihan Jin and Lin Tian of UC Davis, Hongbin Yang of Zhejiang University in Hangzhou, China, Eric Hu, Jonathan Read, and Lilly Tang of UC Berkeley, and Charlotte Seng, Tamás Lukacsovich and Csaba Földy of the University of Zurich, Switzerland.
Funding: The work was supported by the McKnight Foundation, One Mind Foundation, Weill Neurohub, Rita Allen Foundation, Wayne and Gladys Valley Foundation and National Institutes of Health ( R01DA042889, U01NS120820, U01NS113295, R01NS121231, R01DA049787 ).
The National Alliance for Research on Schizophrenia and Depression presented Shimoni with a Young Investigator Award.
About this news about neuroscience and obesity
Author: Robert Sanders
Source: UC Berkeley
Contact: Robert Sanders – UC Berkeley
Image: The image is credited to Neuroscience News
Original research: Free of charge.
Stephan Lammel and colleagues ‘” Changes in neurotensin signaling drive hedonic devaluation in obesity.” Nature
Abstract
Hedonic devaluation is caused by changes in neurotensin signaling in obesity.
Calorie-rich foods, especially those high in fat and sugar, evoke pleasure in both people and animals. However, prolonged consumption of such foods may reduce their hedonic value, potentially contributing to obesity.
On a chronic high-fat diet ( HFD)-fed mouse, we used this study to investigate this phenotype. In a no-effort setting, these mice showed less interest in calorie-rich foods despite choosing high-fat foods over regular chow in their home cages.
This paradoxical decrease in hedonic feeding has been reported previously, but its neurobiological basis remains unclear.
We discovered that hedonic feeding behaviors were encoded by neurons in the lateral nucleus accumbens ( NAcLat ) projecting to the ventral tegmental area (VTA ) in mice on regular diets. This behavior was lessened and disconnected in HFD mice from neural activity.
Optogenetic stimulation of the NAcLat→VTA pathway increased hedonic feeding in mice on regular diet but not in HFD mice, though this behaviour was restored when HFD mice returned to a regular diet. In the NAcLatVTA pathway, HFD mice showed decreased neurotensin expression and release.
Additionally, optogenetically induced hedonic feeding behavior was halted by neurotensin knockout in the NAcLat and neurotensin receptor blockade in the VTA.
Enhancing neurotensin signalling via overexpression normalized aspects of diet-induced obesity, including weight gain and hedonic feeding.
Together, our findings reveal a neural circuitry that links obesity and the devaluation of hedonic foods.
